Exosomes: the next frontier in vaccine development and delivery

Exosomes are small disk-shaped extracellular vesicles (EVs) that are naturally released into the environment by different types of cells. Exosomes range from 30-150 nm in size and contain complex RNA and proteins. They are widely found in body fluids such as blood, saliva, urine and breast milk and participate in cell communication by functioning as cell messengers. Almost all cell types can transmit information and exchange substances through the production and release of exosomes to regulate proliferation, differentiation, apoptosis, the immune response, inflammation, and other biological functions. Because exosomes exist widely in various body fluids, they are easy to obtain and detect and have the potential for use in disease diagnosis and prognosis detection. Exosomes can be genetically fused with targeted proteins, enhancing their biocompatibility and immunogenicity. Therefore, exosomes are the preferred vector tools for vaccines. In this review, we describe the characteristics of exosomes and discuss their unique and ambiguous functions in the immune microenvironment after infection. In this regard, we explored the ability of exosomes to carry immunogenic virus antigens and to establish adaptive immune responses. Exosomes can provide an interesting platform for antigen presentation and since vaccines are a powerful method for the prevention of infectious diseases, we further review the advantages and disadvantages of the use of exosomes in vaccine preparation. Overall, exosomes are emerging as a promising avenue for vaccine development

PolySi-SiO 2 -ZrO 2 -SiO 2 -Si Flash Memory Incorporating a Sol-Gel-Derived ZrO 2 Charge Trapping Layer

In this paper, we propose a method for depositing the charge trapping layer of a high-k polySi-SiO 2 -ZrO 2 -SiO 2 -Si ͑SOZOS͒ memory device. In this approach, the trapping layer was formed through simple two steps: ͑i͒ spin-coating of the ZrCl 4 precursor and ͑ii͒ rapid thermal annealing for 1 min at 900°C under an oxygen atmosphere. The morphology of the ZrO 2 charge trapping layer was confirmed through X-ray photoemission spectroscopy analysis. The sol-gel-derived layer exhibited improved charge trapping in the SOZOS memory device, resulting in a threshold voltage shift of 2.7 V in the I d -V g curve, P/E ͑program/erase͒ speeds as fast as 0.1 ms, good data retention up to 10 4 s ͑only a 5% charge loss due to deep trapping in the ZrO 2 layer͒, and good endurance ͑no memory window narrowing after 10 5 P/E cycles͒. © 2006 The Electrochemical Society. ͓DOI: 10.1149/1.2337846͔ All rights reserved. The first floating-gate ͑FG͒ nonvolatile semiconductor memory was invented by Sze and Kahng in 1967. 1 Conventional FG memory uses polysilicon as a charge-storage layer surrounded by the dielectric. 2 Although floating-gate structures can achieve high densities and good program/erase ͑P/E͒ speeds and exhibit good reliability in portable flash memory devices, there are concerns regarding the ability to scale up their production. 3 When the tunneling oxide thickness is below 10 nm, the storage charge in the FG leaks readily because defects form in the tunneling oxide after repeated write-erase cycles or through direct tunneling of the current. PolySi-oxide-nitride-oxide-silicon ͑SONOS͒ memory devices have been studied recently as an approach to solving the issue of scaling FG memory. 3 Because of their spatially isolated deep-level traps, SONOS memories exhibit better charge retention than do FG memories that have a bitcell tunneling oxide layer thinner than 10 nm. As a result, a single defect in the tunneling oxide will not cause the discharge of the memory cell. 3 SONOS memory devices use silicon nitride as a charge trapping layer; the conduction band offset between the tunneling oxide and nitride is 1.05 eV. When a positive voltage is applied on the gate, the band bends downward so that the electrons in the Si subconduction band will tunnel through the tunneling oxide and a portion of the nitride will become trapped in the charge trapping layer. Before they become trapped in the nitride, the electrons must tunnel through a portion of the nitride, which degrades the program speed. In addition, because the conduction band offset of the nitride is only 1.05 eV, back tunneling of the trapped electron may also occur. To solve these problems, high-k materials are potential candidates to replace the traditional silicon nitride as the charge trapping layer. The advantages of using high-k materials are the larger band offset with the tunneling oxide and the greater number of trapping sites than those found in silicon nitride. For an HfO 2 high-k material, the conduction band offset between the tunneling oxide and HfO 2 is 1.6 eV. When programming, the electron will tunnel through a shorter distance in HfO 2 than in the nitride to become trapped. This feature can be exploited to achieve high P/E speeds. Thus, it will be beneficial to use a high-k material as the charge trapping layer in a SONOS-type memory device, provided that there are many deep-level trapping sites in the high-k material. Many technologies have been developed recently for the deposition of high-k layers onto tunneling oxides, 7-10 including atomic layer deposition ͑ALD͒, metallorganic chemical vapor deposition ͑MOCVD͒, and physical vapor deposition ͑PVD͒. In the ALD method, ZrCl 4 and H 2 O are used to prepare the ZrO 2 films. For the PVD process, a zirconium metal target is used for sputtering under ambient oxygen to deposit the ZrO 2 films. In the CVD method, ZrCl 4 is used as a precursor to deposit ZrO 2 films. Recently, we proposed the first so-called sol-gel spin-coating method for the deposition of the thin film. 11 Sol-gel spin-coating methods use metal halides hydrolyzed in organic or colloidal solvents to form precursor compounds that undergo hydrolysis, condensation, and polymerization to form metal-oxide networks. The advantages of using sol-gel methods to fabricate high-k films are that they are cheaper than ALD, PVD, and MOCVD approaches, and that various types of thin films can be synthesized. To the best of our knowledge, sol-gel spin-coating of a high-k film has yet to be reported for the preparation of charge trapping layers for flash memory devices. In this paper, we describe the fabrication of a polySi-SiO 2 -ZrO 2 -SiO 2 -Si ͑SOZOS͒ flash memory device prepared through the deposition of ZrCl 4 using the sol-gel spin-coating method and subsequent rapid thermal annealing ͑RTA͒. We performed physical and electrical analyses, including X-ray photoemission spectroscopy ͑XPS͒, I d -V g , retention, and P/E speed measurements, to evaluate the performance of the sol-gel ZrO 2 films for their potential use as charge trapping layers in SOZOS memory devices. Experimental ZrCl 4 ͑99.5%, Aldrich, USA͒ was used as the synthetic precursor of the zirconia. A mother sol solution was first prepared by dissolving ZrCl 4 in isopropanol ͑IPA; Fluka; water content Ͻ0.1%͒ under vigorous stirring in an ice bath. The sol solution was obtained by fully hydrolyzing ZrCl 4 with a stoichiometric quantity of water in IPA to yield a Zr:IPA molar ratio of 1:1000. The fabrication of the sol-gel spin-coated SOZOS memory began with LOCOS isolation process on p-type 150 mm silicon ͑100͒ substrate. At first, a 4 nm tunneling oxide layer was grown thermally at 925°C through furnace oxidation. The Zr:IPA solution ͑molar ratio: 1:1000͒ was coated using a spin-coater at 3000 rpm for 60 s at 25°C. A TEL Clean Track model-MK8 ͑Japan͒ spin-coater was used. The as-deposited thin film was initially baked at 200°C for 10 min to perform densification, followed by high-k RTA for 1 min in an O 2 atmosphere to form the ZrO 2 charge trapping layer. The film thickness, measured using an ellipsometer, was 10 nm. A 30 nm thick blocking oxide was deposited using high-density-plasmaenhanced chemical vapor deposition ͑HDPCVD͒, followed by deposition of a poly-Si gate ͑200 nm͒. After gate deposition, the following processes were applied to fabricate the SOZOS memory: * Electrochemical Society Active Member.

Modeling, Design, and Implementation of a Cloud Workflow Engine Based on Aneka

This paper presents a Petri net-based model for cloud workflow which plays a key role in industry. Three kinds of parallelisms in cloud workflow are characterized and modeled. Based on the analysis of the modeling, a cloud workflow engine is designed and implemented in Aneka cloud environment. The experimental results validate the effectiveness of our approach of modeling, design, and implementation of cloud workflow

Effect of Water Saturation on Gas-Accessible Effective Pore Space in Gas Shales

AbstractThe existence and content of water will certainly affect the effective pore space of shales and therefore is a key point for the evaluation of in-situ gas content and gas flow capacity of shale reservoirs. In order to reasonably evaluate the gas storage and flow capacities of water-bearing shale reservoirs, the effect of water on the effective pore space of shales needs to be understood. In this study, the Upper Permian Longtan shale in the southeastern Sichuan Basin, China, was selected as an example to conduct nuclear magnetic resonance cryoporometry (NMRC) measurements under different water saturation levels. The gas-accessible effective pore spaces in shales under different water saturation levels were quantified, and the effect of water saturation on gas-accessible effective pore space in shales was investigated. The results show that water plays an important role in the gas-accessible effective pore space of shales. When the Longtan shale increases from a dry state to a water saturation of 65%, 75%, and 90%, the gas-accessible effective pore volume decreases by 35%-60% (average 46.3%), 50%-70% (average 58.8%), and 65%-82% (average 75.8%), respectively. Water has an effect on the gas-accessible effective pore space regardless of pore size, and the effect is the strongest in the 4-100 nm range, which may be mainly due to the high content of clay minerals in the Longtan shale. Our studies are of important theoretical significance and application prospects for accurately evaluating the gas-accessible effective pore space of gas shales under actual geological conditions

High-mobility graphene on liquid p-block elements by ultra-low-loss CVD growth

The high-quality and low-cost of the graphene preparation method decide whether graphene is put into the applications finally. Enormous efforts have been devoted to understand and optimize the CVD process of graphene over various d-block transition metals (e.g. Cu, Ni and Pt). Here we report the growth of uniform high-quality single-layer, single-crystalline graphene flakes and their continuous films over p-block elements (e.g. Ga) liquid films using ambient-pressure chemical vapor deposition. The graphene shows high crystalline quality with electron mobility reaching levels as high as 7400 cm2 V−1s−1 under ambient conditions. Our employed growth strategy is ultra-low-loss. Only trace amounts of Ga are consumed in the production and transfer of the graphene and expensive film deposition or vacuum systems are not needed. We believe that our research will open up new territory in the field of graphene growth and thus promote its practical application

PALMD regulates aortic valve calcification via altered glycolysis and NF-κB-mediated inflammation

Recent genome-wide association and transcriptome-wide association studies have identified an association between the PALMD locus, encoding palmdelphin, a protein involved in myoblast differentiation, and calcific aortic valve disease (CAVD). Nevertheless, the function and underlying mechanisms of PALMD in CAVD remain unclear. We herein investigated whether and how PALMD affects the pathogenesis of CAVD using clinical samples from CAVD patients and a human valve interstitial cell (hVIC) in vitro calcification model. We showed that PALMD was upregulated in calcified regions of human aortic valves and calcified hVICs. Furthermore, silencing of PALMD reduced hVIC in vitro calcification, osteogenic differentiation, and apoptosis, whereas overexpression of PALMD had the opposite effect. RNA-Seq of PALMD-depleted hVICs revealed that silencing of PALMD reduced glycolysis and nuclear factor-κB (NF-κB)–mediated inflammation in hVICs and attenuated tumor necrosis factor α–induced monocyte adhesion to hVICs. Having established the role of PALMD in hVIC glycolysis, we examined whether glycolysis itself could regulate hVIC osteogenic differentiation and inflammation. Intriguingly, the inhibition of PFKFB3-mediated glycolysis significantly attenuated osteogenic differentiation and inflammation of hVICs. However, silencing of PFKFB3 inhibited PALMD-induced hVIC inflammation, but not osteogenic differentiation. Finally, we showed that the overexpression of PALMD enhanced hVIC osteogenic differentiation and inflammation, as opposed to glycolysis, through the activation of NF-κB. The present study demonstrates that the genome-wide association– and transcriptome-wide association–identified CAVD risk gene PALMD may promote CAVD development through regulation of glycolysis and NF-κB–mediated inflammation. We propose that targeting PALMD-mediated glycolysis may represent a novel therapeutic strategy for treating CAVD